tbuckley/cabot-search huggingface dataset:
Transcarotid Artery Revascularization for Stroke Prevention—Multiple Elephants in the Room
Authors: Seemant Chaturvedi
Journal: JAMA Neurology (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
Gut microbiota modulates visceral sensitivity through calcitonin gene-related peptide (CGRP) production
Authors: Julien Pujo, Giada De Palma, Jun Lu, Heather J. Galipeau, Michael G. Surette, Stephen M. Collins, Premysl Bercik
Journal: Gut Microbes (2023)

Abdominal pain is common in patients with gastrointestinal disorders, but its pathophysiology is unclear, in part due to poor understanding of basic mechanisms underlying visceral sensitivity. Accumulating evidence suggests that gut microbiota is an important determinant of visceral sensitivity. Clinical and basic research studies also show that sex plays a role in pain perception, although the precise pathways are not elucidated. We investigated pain responses in germ-free and conventionally raised mice of both sexes, and assessed visceral sensitivity to colorectal distension, neuronal excitability of dorsal root ganglia (DRG) neurons and the production of substance P and calcitonin gene-related peptide (CGRP) in response to capsaicin or a mixture of G-protein coupled receptor (GPCR) agonists. Germ-free mice displayed greater in vivo responses to colonic distention than conventional mice, with no differences between males and females. Pretreatment with intracolonic capsaicin or GPCR agonists increased responses in conventional, but not in germ-free mice. In DRG neurons, gut microbiota and sex had no effect on neuronal activation by capsaicin or GPCR agonists. While stimulated production of substance P by DRG neurons was similar in germ-free and conventional mice, with no additional effect of sex, the CGRP production was higher in germ-free mice, mainly in females. Absence of gut microbiota increases visceral sensitivity to colorectal distention in both male and female mice. This is, at least in part, due to increased production of CGRP by DRG neurons, which is mainly evident in female mice. However, central mechanisms are also likely involved in this process.
A comprehensive and systemic review of ginseng‐based nanomaterials: Synthesis, targeted delivery, and biomedical applications
Authors: Sri Renukadevi Balusamy, Haribalan Perumalsamy, Md. Amdadul Huq, Tae Hyun Yoon, Ivan Mijakovic, Lakshmi Thangavelu, Deok Chun Yang, Shadi Rahimi
Journal: Medicinal Research Reviews (2023)

Abstract Among 17 Panax species identified across the world, Panax ginseng (Korean ginseng), Panax quinquefolius (American ginseng), and Panax notoginseng (Chinese ginseng) are highly recognized for the presence of bioactive compound, ginsenosides and their pharmacological effects. P. ginseng is widely used for synthesis of different types of nanoparticles compared to P. quinquefolius and P. notoginseng . The use of nano‐ginseng could increase the oral bioavailability, membrane permeability, and thus provide effective delivery of ginsenosides to the target sites through transport system. In this review, we explore the synthesis of ginseng nanoparticles using plant extracts from various organs, microbes, and polymers, as well as their biomedical applications. Furthermore, we highlight transporters involved in transport of ginsenoside nanoparticles to the target sites. Size, zeta potential, temperature, and pH are also discussed as the critical parameters affecting the quality of ginseng nanoparticles synthesis.
Tracing Founder Mutations in Circulating and Tissue-Resident Follicular Lymphoma Precursors
Authors: Joseph G. Schroers-Martin, Joanne Soo, Gabriel Brisou, Florian Scherer, David M. Kurtz, Brian J. Sworder, Michael S. Khodadoust, Michael C. Jin, Agnès Bru, Chih Long Liu, Henning Stehr, Paolo Vineis, Yasodha Natkunam, Lauren R. Teras, Joo Y. Song, Bertrand Nadel, Maximilian Diehn, Sandrine Roulland, Ash A. Alizadeh
Journal: Cancer Discovery (2023)

Follicular lymphomas (FL) are characterized by BCL2 translocations, often detectable in blood years before FL diagnosis, but also observed in aging healthy individuals, suggesting additional lesions are required for lymphomagenesis. We directly characterized early cooperating mutations by ultradeep sequencing of prediagnostic blood and tissue specimens from 48 subjects who ultimately developed FL. Strikingly, CREBBP lysine acetyltransferase (KAT) domain mutations were the most commonly observed precursor lesions, and largely distinguished patients developing FL (14/48, 29%) from healthy adults with or without detected BCL2 rearrangements (0/13, P = 0.03 and 0/20, P = 0.007, respectively). CREBBP variants were detectable a median of 5.8 years before FL diagnosis, were clonally selected in FL tumors, and appeared restricted to the committed B-cell lineage. These results suggest that mutations affecting the CREBBP KAT domain are common lesions in FL cancer precursor cells (CPC), with the potential for discriminating subjects at risk of developing FL or monitoring residual disease.Our study provides direct evidence for recurrent genetic aberrations preceding FL diagnosis, revealing the combination of BCL2 translocation with CREBBP KAT domain mutations as characteristic committed lesions of FL CPCs. Such prediagnostic mutations are detectable years before clinical diagnosis and may help discriminate individuals at risk for lymphoma development. This article is highlighted in the In This Issue feature, p. 1275.
MEN1 Degradation Induced by Neddylation and the CUL4B–DCAF7 Axis Promotes Pancreatic Neuroendocrine Tumor Progression
Authors: Junfeng Xu, Zeng Ye, Qifeng Zhuo, Heli Gao, Yi Qin, Xin Lou, Wuhu Zhang, Fei Wang, Yan Wang, Desheng Jing, Guixiong Fan, Yue Zhang, Xuemin Chen, Jie Chen, Xiaowu Xu, Xianjun Yu, Shunrong Ji
Journal: Cancer Research (2023)

Abstract Pancreatic neuroendocrine tumors (PanNET) are a group of rare sporadic malignant tumors in the pancreas. MEN1 is the most frequently mutated gene in PanNETs. The MEN1-encoded protein is a typical tumor suppressor that forms a complex with epigenetic and transcription factors and is an attractive target for therapeutic interventions for patients with PanNET. A better understanding of the regulation of MEN1 protein expression in PanNETs could identify strategies for targeting MEN1. Here, we found that the neddylation pathway and DCAF7-mediated ubiquitination regulated MEN1 protein expression. Increased expression of members of the neddylation pathway and DCAF7 was found in PanNET tissues compared with paired-adjacent tissues and was associated with poor prognosis in patients with PanNET. Suppression of neddylation using the neddylation inhibitor MLN4924 or RNA interference significantly induced MEN1 accumulation and repressed cancer-related malignant phenotypes. CUL4B and DCAF7 promoted MEN1 degradation by binding and catalyzing its ubiquitination. In PanNET cells resistant to everolimus, a pharmacologic mTOR inhibitor widely used for advanced PanNET patient treatment, the downregulation of DCAF7 expression overcame resistance and synergized with everolimus to suppress mTOR activation and to inhibit cancer cell growth. The effects of DCAF7 loss could be counteracted by the simultaneous knockdown of MEN1 both in vitro and in vivo. The inverse correlation between DCAF7 and MEN1 was further validated in clinical specimens. This study revealed that the posttranslational control of MEN1 expression in PanNET is mediated by neddylation and the CUL4B–DCAF7 axis and identifies potential therapeutic targets in patients with MEN1-associated PanNET. Significance: Identification of neddylation and ubiquitination pathways that regulate MEN1 protein stability provides an opportunity for therapeutic interventions for treating patients with pancreatic neuroendocrine tumors.
Perioperative Risk Assessment and Avoiding Overuse of Anesthesia Care for Routine Cataract Surgery
Authors: Achia Nemet, Raimo Tuuminen
Journal: JAMA Internal Medicine (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Effectiveness of Structured Care Coordination for Children With Medical Complexity
Authors: Eyal Cohen, Samantha Quartarone, Julia Orkin, Myla E. Moretti, Abby Emdin, Astrid Guttmann, Andrew R. Willan, Nathalie Major, Audrey Lim, Sanober Diaz, Lisa Osqui, Joanna Soscia, Longdi Fu, Sima Gandhi, Anna Heath, Nora Fayed
Journal: JAMA Pediatrics (2023)

Importance Children with medical complexity (CMC) have chronic conditions and high health needs and may experience fragmented care. Objective To compare the effectiveness of a structured complex care program, Complex Care for Kids Ontario (CCKO), with usual care. Design, Setting, and Participants This randomized clinical trial used a waitlist variation for randomizing patients from 12 complex care clinics in Ontario, Canada, over 2 years. The study was conducted from December 2016 to June 2021. Participants were identified based on complex care clinic referral and randomly allocated into an intervention group, seen at the next available clinic appointment, or a control group that was placed on a waitlist to receive the intervention after 12 months. Intervention Assignment of a nurse practitioner–pediatrician dyad partnering with families in a structured complex care clinic to provide intensive care coordination and comprehensive plans of care. Main Outcomes and Measures Co-primary outcomes, assessed at baseline and at 6, 12, and 24 months postrandomization, were service delivery indicators from the Family Experiences With Coordination of Care that scored (1) coordination of care among health care professionals, (2) coordination of care between health care professionals and families, and (3) utility of care planning tools. Secondary outcomes included child and parent health outcomes and child health care system utilization and cost. Results Of 144 participants randomized, 141 had complete health administrative data, and 139 had complete baseline surveys. The median (IQR) age of the participants was 29 months (9-102); 83 (60%) were male. At 12 months, scores for utility of care planning tools improved in the intervention group compared with the waitlist group (adjusted odds ratio, 9.3; 95% CI, 3.9-21.9; P &amp;amp;lt; .001), with no difference between groups for the other 2 co-primary outcomes. There were no group differences for secondary outcomes of child outcomes, parent outcomes, and health care system utilization and cost. At 24 months, when both groups were receiving the intervention, no primary outcome differences were observed. Total health care costs in the second year were lower for the intervention group (median, CAD$17 891; IQR, 6098-61 346; vs CAD$37 524; IQR, 9338-119 547 [US $13 415; IQR, 4572-45 998; vs US $28 136; IQR, 7002-89 637]; P = .01). Conclusions and Relevance The CCKO program improved the perceived utility of care planning tools but not other outcomes at 1 year. Extended evaluation periods may be helpful in assessing pediatric complex care interventions. Trial Registration ClinicalTrials.gov Identifier: NCT02928757
Reduced versus maximum tolerated methotrexate dose concomitant with adalimumab in patients with rheumatoid arthritis (MIRACLE): a randomised, open-label, non-inferiority trial
Authors: Hiroya Tamai, Kei Ikeda, Toshiaki Miyamoto, Hiroaki Taguchi, Chang-Fu Kuo, Kichul Shin, Shintaro Hirata, Yutaka Okano, Shinji Sato, Hidekata Yasuoka, Masataka Kuwana, Tomonori Ishii, Hideto Kameda, Toshihisa Kojima, Takehiro Taninaga, Masahiko Mori, Hideaki Miyagishi, Yasunori Sato, Wen-Chan Tsai, Tsutomu Takeuchi, Yuko Kaneko, Keisuke Izumi, Yasushi Kondo, Keiko Yoshimoto, Takahisa Gono, Sung-Hwan Park, Han Joo Baek, Yun Jong Lee, In Ah Choi, Jinhyun Kim, Ping-Ning Hsu, Chun-Ming Huan, Meng-Yu Weng, Wan-Yu Sung, Tien-Tsai Cheng
Journal: The Lancet Rheumatology (2023)
Impact of <i>TP53</i> on outcome of patients with myelofibrosis undergoing hematopoietic stem cell transplantation
Authors: Nico Gagelmann, Anita Badbaran, Rachel B Salit, Thomas Schroeder, Carmelo Gurnari, Simona Pagliuca, Victoria Panagiota, Christina Rautenberg, Bruno Cassinat, Felicitas R. Thol, Christine Wolschke, Marie Robin, Michael Heuser, Marie-Thérèse Rubio, Jaroslaw P. Maciejewski, Hans Christian Reinhardt, Bart L Scott, Nicolaus Kröger
Journal: Blood (2023)

TP53 mutations (TP53MT) have been associated with poor outcomes in various hematologic malignancies, but no data exist on its role in patients with myelofibrosis undergoing hematopoietic stem cell transplantation (HSCT). Here, we took advantage of a large international multicenter cohort to evaluate the role of TP53MTin this setting. Among 349 included patients, 49 (13%) had detectable TP53MT, of whom 30 showed a multi-hit configuration. Median variant allele frequency was 20.3%. Cytogenetic risk was favorable (71%), unfavorable (23%), and very high (6%), with complex karyotype present in 36 patients (10%). Median survival of TP53MT patients was 1.5 years vs 13.5 years for the TP53WT group (P&amp;lt;0.001). Outcome was driven by multi-hit TP53MT constellation (P&amp;lt;0.001), showing 6-year survival of 56% for single-hit vs 25% for multi-hit TP53MT carriers vs 64% for TP53WT. Outcome was independent of current transplant-specific risk factors and conditioning intensity. Similarly, cumulative incidence of relapse was 17% for single-hit vs 52% for multi-hit vs 21% for TP53WT. Ten patients with TP53MT (20%) presented as leukemic transformation vs only 7 (2%) in the TP53WT group (P&amp;lt;0.001). Out of the 10 patients with TP53MT, 8 showed multi-hit constellation. Median time to leukemic transformation was shorter for multi-and single-hit TP53MT (0.7 and 0.5 years, respectively) vs 2.5 years for TP53WT. In summary, multi-hit TP53MT represents a very high-risk group in myelofibrosis patients undergoing HSCT, whereas single-hit TP53MTalone showed similar outcome to non-mutated patients, informing prognostication for survival and relapse together with current transplant-specific tools.
Five cities, from Athens to Montevideo, are recognised for public health work
Authors: Elisabeth Mahase
Journal: BMJ (2023)

Five cities, from Athens to Montevideo, are recognised for public health work Elisabeth MahaseFive cities across the globe have been awarded $150 000 at the first Partnership for Healthy Cities Summit, to continue their work in preventing noncommunicable diseases (NCDs) and injuries.The summit, which took place in London on 15 March, saw global health leaders and mayors from more than 50 major cities come together to discuss urgent public health concerns and best practices that save lives and create healthier cities.The winning cities included Athens, Greece, for increasing access to naloxone for opioid overdoses; Bengaluru, India, for reducing smoking in public places; and Vancouver, Canada, for launching an online public health data tool that tracks population health indicators, as well as working with urban indigenous communities to inform data management.Other cities recognised were Mexico City, where the introduction of a bike path on a busy road led to a 275% increase in cyclists, and Montevideo, Uruguay, which has established nutritional standards for the preparation and sale of food in government agency offices and some public universities.The Partnership for Healthy Cities was founded in 2017 and is made up of 70 cities around the world who work together to prevent NCDs and injuries, which are responsible for over 80% of all deaths globally.Mayor of London Sadiq Khan said, "I'm delighted to be joining mayors from around the world to tackle some of the biggest problems facing our cities.The health of our citizens is a city's greatest asset so I'm taking bold steps to invest in the health of Londoners, such as restricting junk food advertising across the Transport for London network and expanding the ultra low emission zone, which will mean five million more Londoners will be able to breathe cleaner air."These initiatives are not only improving the health of Londoners, but alleviating pressure on our health service and ensuring that future generations can thrive.Improving the health of Londoners will always be at the heart of my vision to build a safer and more prosperous London for everyone.
Assessing Heterogeneity of Treatment Effect in Real-World Data
Authors: Jodi B. Segal, Ravi Varadhan, Rolf H.H. Groenwold, Nicholas C. Henderson, Xiaojuan Li, Kaori Nomura, Sigal Kaplan, Shirin Ardeshirrouhanifard, James Heyward, Fredrik Nyberg, Mehmet Burcu
Journal: Annals of Internal Medicine (2023)

Increasing availability of real-world data (RWD) generated from patient care enables the generation of evidence to inform clinical decisions for subpopulations of patients and perhaps even individuals. There is growing opportunity to identify important heterogeneity of treatment effects (HTE) in these subgroups. Thus, HTE is relevant to all with interest in patients' responses to interventions, including regulators who must make decisions about products when signals of harms arise postapproval and payers who make coverage decisions based on expected net benefit to their beneficiaries. Prior work discussed HTE in randomized studies. Here, we address methodological considerations when investigating HTE in observational studies. We propose 4 primary goals of HTE analyses and the corresponding approaches in the context of RWD: to confirm subgroup effects, to describe the magnitude of HTE, to discover clinically important subgroups, and to predict individual effects. We discuss other possible goals including exploring prognostic score- and propensity score-based treatment effects, and testing the transportability of trial results to populations different from trial participants. Finally, we outline methodological needs for enhancing real-world HTE analysis.
Use of Daratumumab in Patients With Previously Treated Multiple Myeloma
Authors: Ashwin P. Patel
Journal: Journal of Clinical Oncology (2023)

Sonneveld et al 1 reported reduced mortality and improved overall survival with daratumumab 1 bortezomib 1 dexamethasone (D-Vd) treatment compared with bortezomib 1 dexamethasone (Vd) in patients with refractory or relapsed multiple myeloma.More information/explanation may be helpful to understand the results and the conclusions reported in the article.
Lowering Serum Urate With <scp>Urate‐Lowering</scp> Therapy to Target and Incident Fracture Among People With Gout
Authors: Jie Wei, Hyon K. Choi, Nicola Dalbeth, Nancy E. Lane, Jing Wu, Houchen Lyu, Chao Zeng, Guanghua Lei, Yuqing Zhang
Journal: Arthritis & Rheumatology (2023)

Objective Gout is associated with a higher risk of fracture; however, findings on the associations of hyperuricemia and urate‐lowering therapy (ULT) with the risk of fracture have been inconsistent. We examined whether lowering serum urate (SU) levels with ULT to a target level (i.e., &lt;360 μmoles/liter) reduces the risk of fracture among individuals with gout. Methods We emulated analyses of a hypothetical target trial using a “cloning, censoring, and weighting” approach to examine the association between lowering SU with ULT to the target levels and the risk of fracture using data from The Health Improvement Network, a UK primary care database. Individuals with gout who were age 40 years or older and for whom ULT was initiated were included in the study. Results Among 28,554 people with gout, the 5‐year risk of hip fracture was 0.5% for the “achieving the target SU level” arm and 0.8% for the “not achieving the target SU level” arm. The risk difference and hazard ratio for the “achieving the target SU level” arm was –0.3% (95% confidence interval [95% CI] –0.5%, –0.1%) and 0.66 (95% CI 0.46, 0.93), respectively, compared with the “not achieving the target SU level” arm. Similar results were observed when the associations between lowering SU level with ULT to the target levels and the risk of composite fracture, major osteoporotic fracture, vertebral fracture, and nonvertebral fracture were assessed. Conclusion In this population‐based study, lowering the SU level with ULT to the guideline‐based target level was associated with a lower risk of incident fracture in people with gout. image
A probable ecologic bias in the article on the progression of knee osteoarthritis: comment on the article by Lo et al
Authors: Hasan Yazici, Hande Ogun, Yusuf Yazici
Journal: Arthritis & Rheumatology (2023)

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